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Through diversity-oriented synthesis, chemists
are achieving more structural complexity than in the early days of
combinatorial chemistry, tackling compounds with multiple stereocenters and
complex, natural product-like libraries. Preparation of structurally complex
and diverse compounds results in a broader population of chemical space and
facilitates effective probing of biological space. Structural complexity is
very significant because many of the small molecules known to disrupt
protein-protein interactions are complex natural products or natural
product-like compounds. The potential for therapeutic development depends
however not only upon structural complexity but also upon synthetic
accessibility and scalability. Achieving this difficult balance demands
innovative chemistry such as that described at this symposium. Attend this
event to hear the latest developments in diversity-oriented synthesis and its
impact on drug development.
Who Should Attend
Vice Presidents, Directors, Research Scientists in Combinatorial Chemistry,
Natural Product Chemistry, Discovery Chemistry and Medicinal Chemistry |
| Keynote
Presentations |
Diversity-Oriented Synthesis, Chemical Genetics, and ChemBank
Dr. Stuart L. Schreiber, Harvard Institute of Chemistry & Cell
Biology (ICCB), Harvard University
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Peptide
Morphing
Dr. Gregory Verdine, Department of
Chemistry and Chemical Biology, Harvard
University |
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Advisory
Committee
Dr. Prabhat Arya, Chemical Biology Program, Steacie Institute for
Molecular Sciences, National Research Council of Canada
Dr. Neerja Bhatnagar, Head, Natural Product Chemistry, DI&A/Chemistry/High
Performance Unit, Aventis
Dr. Larry Hardy, Head of Biology, Aurigene Discovery Technologies
Dr David R. Spring, Department of Chemistry, University of Cambridge
Dr. Derek S. Tan, Laboratory of Chemistry & Chemical Genetics; Assistant
Member, Molecular Pharmacology & Chemistry Program; Member,
Tri-Institutional Training Program in Chemical Biology, Memorial Sloan-Kettering
Cancer Center |
- Speakers from
Aventis, Amgen, AstraZeneca, Bayer,
Novartis, Pfizer, Wyeth
- Boston's
Chemistry Centers of Excellence
Boston College | Boston University | Harvard
University
- Facilitated
Roundtable Discussion
- Judged Poster
Contest
- Exhibit Hall
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THURSDAY,
OCTOBER 9
8:00-8:30am Coffee and Registration
Boston's
Chemistry Centers Of Excellence
8:30-8:40 Chairperson's Remarks
Dr. Larry Hardy, Head of Biology, Aurigene Discovery Technologies
8:40-9:40 KEYNOTE ADDRESS
Diversity-Oriented Synthesis, Chemical
Genetics, and ChemBank
Dr. Stuart L. Schreiber, Investigator, Howard Hughes Medical Institute,
Morris Loeb Professor and Chair, Chemistry & Chemical Biology, Director,
Initiative for Chemical Genetics (ICG), Co-Director, Harvard Institute of
Chemistry & Cell Biology (ICCB) Harvard University
To explore biology systematically using small molecules will require three
advances. We need the right set of small molecule modulators. The current set
populates chemical descriptor space densely in a limited number of regions and
sparsely in many promising regions. Diversity-oriented synthesis aims to address
this need. We need to develop methods to measure the outcome of small
molecule-based perturbations globally. Chemical genetics aims to address this
second need. Finally, we need to manage the data in a way that allows the
outcome of all experiments to be at least as useful as the outcome of individual
experiments. ChemBank has been established to address this last need. Elements
of these three research advances will be presented. |
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9:40-10:10 Expanded Chemical Diversity
Using Stereocontrolled Synthesis
Dr. John A. Porco, Jr., Department of Chemistry, Boston University
Projects underway at the Boston University Center
for Chemical
Methodology and Library Development (CMLD-BU) involve
stereochemi-cal
and positional variation within the molecular framework
as diversity
elements for library design. This seminar will focus on
examples of this
strategy, including novel scaffolds, tools, diversity
reagents, and related
strategies for the synthesis of complex molecule
libraries
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10:10-11:10 Coffee Break, Poster and Exhibit
Viewing |
11:10-11:40 Diversity-Oriented Catalyst
Discovery for Diversity-Oriented Synthesis
Dr. Scott Miller, Professor of Chemistry, Boston College
The development of combinatorial techniques to assist enantioselective
catalyst discovery will be described. In addition, applications of the
techniques and catalysts to the synthesis of biologically active molecules will
be discussed. |
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11:40-12:10 Panel Discussion (Q&A with the
above speakers)
| 12:10-1:40 Lunch, Poster and Exhibit Viewing
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The Pharmaceutical Focus
1:40-1:50 Chairperson's Remarks
Dr. Norton Peet, CEO, Aurigene Discovery Technologies
1:50-2:10 Computer Assisted MPS Approaches to
Disparate Core Synthesis
Dr. William F. Michne, Senior Principal Scientist, AstraZeneca
Our efforts to resynthesize depleted compounds in structurally diverse
biology-based sets led us to explore several approaches to diversity-oriented
synthesis. In particular, novel software assisted organization of multiparallel
synthesis to enable efficient preparation of compounds with disparate cores will
be described.
2:10-2:40 Rapid Assembley of Molecular
Diversity via Exploitation of Isocyanide based Multi-component Reactions
Dr. Chris Hulme, Head of Combinatorial Chemistry, Amgen
This talk reviews the development of chemical methodology over the last
several years, concentrating on novel secondary reactions of IMCRs (isocyanide
multi-component reactions) and introduces the UDC (Ugi/De-BOC/Cyclize) &
BIFA (bifunctional approach) concepts applied to IMCR lead generation. With the
advent of functional proteomics delivering hundreds of new targets to drug
discovery, ultra-high-throughput screening and a premium on novel biologically
active entities, it seems reasonable to speculate that the discovery of new
IMCRs will continue, spawning multiple post-condensation possibilities via
secondary reactions. Indeed, from the one-step preparation of local anaesthetic
XylocainTM to the multi-step preparation of the HIV protease inhibitor
CrixivanTM, isocyanide based multicomponent reactions have experienced a
resurgence of interest and appear well positioned for a stronger impact as we
enter the post-genomic era in the new millenium.
2:40-3:10 From Target to Lead - The Impact of
Combinatorial Technologies
Dr. Joszef Aszodi, Site Director, Aventis Combinatorial Technology Center
In its early days, diversity-oriented combinatorial chemistry was conceived
as a tool for complementing drug discovery compound collections in order to
populate new areas of the chemical space that was not covered by historical
libraries. However, over the last few years it has matured into a more powerful
technology that provides the ability to efficiently produce large numbers of
even synthetically challenging lead-like molecules. When combined with other
high throughput tools, these libraries are now delivering high quality lead
compounds. This presentation will describe such a lead discovery engine built
within Aventis and explore its potential application across early drug discovery
from target to lead.
3:10-3:40 Refreshment Break
3:40-4:10 Synthesis of 8-Desbromohinckdentine
A
Dr. William W. McWhorter, Jr., Principal Research Scientist, Pfizer, Inc.
Hinckdentine A, a structurally unique indole alkaloid isolated from the
bryozoan Hincksinoflustra denticulate, contains biologically important
dihydrotryptamine and dihydropyrimidine units within its framework. The
synthesis of the hinckdentine A skeleton features a pinacol-like rearrangement,
which forms the quaternary center of the natural product, and an efficient
seven-membered ring-forming intramolecular aldol condensation as the key steps.
The flexible synthetic route to this fascinating molecular architecture allows
the preparation of an array of novel alkaloid probes of biological space.
4:10-4:40 Diversity Oriented Synthesis for
Pharmaceutically Relevant Molecules
Dr. Michael A. Foley, Vice President, Chemical Technologies, Infinity
Pharmaceuticals
This presentation will cover strategies and methods for thestereoselective
synthesis of pharmaceutically relevant molecules. Thepresentation will also
cover emerging strategies and methods forefficiently extracting the subtle
structure activity relationshipsbetween isomers of stereochemically complex
molecules.
4:40-5:00 Panel Discussion
5:00 Close of the Day
FRIDAY, OCTOBER 10
| 7:30-8:15am Coffee, Technology Workshops |
Sponsored
By: |
An Intelligent Approach to Chemistry Development
The Impact of Drug Discovery Technologies on Reducing Development Time
Presented By Hans Johansson, President & COO, Personal Chemistry |
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Natural Product Diversity
8:30-8:40 Chairperson's Remarks
Dr. Richard Versace, Senior Scientist, Oncology Department, Novartis
Institute for Biomedical Research
8:40-9:10 Future Potential of Natural Products
as Quality Leads, Attempts for a Qualitative and Quantitative Assessment
Dr. Matthias Gehling, Head of Natural Products Research, Bayer AG, Pharma
The importance of natural products as drugs for life science applications
can easily be drawn from actual sales figures of marketed products and their
impact as biochemical tools, as well as inspiring starting point for
chemical/biological optimisation to become a useful product. However, regarding
the identification of new innovative bioactive compounds from nature, the value
assessment of certain biological material towards molecular diversity and thus
improvement of probability of success, is still challenging. This even increases
the intrinsic high costs of this research. This presentation will emphasize the
potential of natural products and will touch on perspectives on how they can
contribute to the value generation chain of the life science industry in the
future.
9:10-9:40 Novel Indole Alkaloid Based
Screening Libraries for Drug Discovery
Dr. Demos Fokas, Senior Investigator, Chemistry, ArQule, Inc.
Polycyclic indole alkaloids continue to be a widely studied class of
compounds both for their biological relevance and structural complexity. These
natural and unnatural indole ring systems are also of interest as the basis for
the creation of primary screening libraries for drug discovery. The synthetic
challenges to access this interesting and diverse class of compounds will be
described along with the application of the chemistry to the automated parallel
synthesis of indole alkaloid libraries.
9:40-10:10 Natural Products Research at
Novartis Pharma
Dr. Frank Petersen, Head, Natural Products Unit, Novartis
The natural products research group sustainably contributes to the
development pipeline of Novartis Pharma. Outlining reasons for the increasing
pressure on drug discovery, concepts are discussed, how pharmaceutical companies
reacts on these challenges in their natural products directions. In the mirror
of concrete examples from Novartis Pharma, it will be discussed, why natural
products are still an still important and productive source for new biologically
active metabolites and innovative drugs.
10:10-10:30 Coffee Break
10:30-11:00 Chemical Novelty and Biological
Relevance of Natural Products
Dr. Dwight Baker, Senior Director, Albany Molecular Research, Inc.
Small molecule natural product compounds have been selected over millions of
years by evolution as effectors of biological processes. Throughout the past few
decades, hundreds of these have been identified as useful therapeutic drugs, or
the starting point for medicinal chemistry programs, for a wide range of human,
animal and plant diseases. Additional novel chemical structures are yet to be
discovered that will be incorporated into tomorrow's medicines. Examples of the
utility and modern approaches to natural product discovery will be reviewed.
11:00-11:30 New Technologies for Natural
Product Discovery
Dr. Frank Koehn, Head of the Natural Products Chemistry Group, Wyeth
The modern drug discovery environment is characterized by a steadily
increasing number of available targets, coupled with a necessity to reduce
Discovery cycle times. In order to be a high-impact component of the accelerated
Discovery process, a natural products program must share the same sense of
urgency and strategic priorities. In this talk we will describe the developent
and application of new methods and technologies which enable the rapid
detection, prioritization, isolation and structure elucidation of relevant
natural product drug leads.
11:30-12:00 Panel Discussion
12:00-1:30 Lunch (on your own)
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Emerging Company Showcase
1:30-1:40 Chairperson's Remarks
Dr. Michael A. Foley
1:40-2:00 Natural Product Scaffolds as the
Core of Drug Discovery
Dr. Larry Hardy
Deconvolution of actives from natural product extracts is highly risky and
very demanding of both time and money. This is why, despite the extensive
history of natural products as sources of therapeutic agents, the pursuit of new
biological sources of drug candidates has been nearly abandoned by many
pharmaceutical companies. Yet the interest in natural compounds remains high. In
this presentation, the intrinsic advantages of leveraging the core structures of
natural products for diversity oriented synthesis in lead generation will be
outlined briefly. We will then describe the parallel hemi-synthetic approach
developed at Aurigene to effectively capture the attractive biological and
physicochemical features of natural product scaffolds, while avoiding the risk
and time bottlenecks of extracts. Several dozen natural product scaffolds with
unique properties are being explored. We recently found that one of these is a
previously unsuspected but significant inhibitor of a therapeutic target enzyme.
The approaches we have developed for small molecule libraries are
cost-effective, efficient, expedient and amenable to solid and solution phase
parallel synthetic methods. Production of the small molecule libraries is guided
by computational estimates of both the chemical diversity and the ADME
properties of the virtual libraries. The synthetic campaign for elaborating one
specific scaffold will be explored in detail, to demonstrate explicitly how a
natural product scaffold can be used as an edifice from which to launch pursuits
of several target proteins.
2:00-2:20 A Systematized Platform for
Exploiting Biosynthesis for DOS Based Drug Discovery
Dr. Michael Chaparian, President & Chief Scientific Officer, SelectX
Pharmaceuticals, Inc.
The de novo biosynthesis of natural products, including glycosylation,
represents the holy grail of complexity generating chemistries that are vital
for DOS based discovery. Biosynthetic examples of DOS include the polyketides
and terpenes, as well as the enormous additional diversity achieved through
glycosylation of virtually all classes of natural products. However,
exploitation of the full power of biosynthetic chemistries has been difficult,
with most successes centered around only simple single-enzyme biotransformations.
We have innovated a systematized integration of informatics, molecular genetics,
and biochemistry to fully exploit the power of biosynthetic chemistries for the
generation of DOS derived small molecule libraries of both natural products and
natural product-like compounds. This multidisciplinary platform is underpinned
by molecular selection, resulting in significant advantages over conventional
screening and rapid scale-up of hits. Example applications of this platform will
be described.
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2:20-2:40 Diversity Oriented Synthesis and
Multiple Reaction Pathway: Strategies to construct diversity by carbon-carbon,
and carbon-het-ero bond formation.
Dr. Zhen Yang, Director of Chemistry, VivoQuest, Inc.
VivoQuest is a small molecule based drug discovery company that utilizes
powerful diversity-oriented synthetic chemistry (“ChemQuest”) for the rapid
discovery and development of drugs to treat a wide variety of indi-cations.
VivoQuest has developed a platform of diverse natural product related
small-molecule libraries. The company’s ChemQuest libraries embody the
structural complexity of natural products, but can be diversi-fied widely,
produced cheaply and subjected to rapid structure/activity optimization.
VivoQuest has surveyed the natural products diversity space and identified
scaffolds or core motifs that tend to recur in potent drugs. The company
has elaborated these core motifs through creative carbon-carbon and carbon-heteroatom
bond forming strategies to synthesize diverse drug-like molecules with natural
product properties. Screening of the ChemQuest libraries in HCV and HIV
discovery programs has yielded attractive hits for advancement in pre-clinical
discovery.
2:40-3:20 Closing Keynote Address
Peptide Morphing
Dr. Gregory Verdine, Erving Professor of Chemistry, and Associate Member,
Department of Molecular and Cellular Biology, Harvard University
We have been exploring the use of a new strategy that we term "peptide
morphing" to generate potent bioactive ligands to peptide receptors. This
strategy entails the use of side-chain information from peptides to program the
synthesis of exhaustively stereodiversified libraries of polyketide-like
molecules. Progress toward the creation of potent, selective ligands for the
Mu-opioid receptor will be reviewed. |
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3:20-3:30 Q&A
3:30 Close of the Conference
| Lead Sponsoring Publication: |
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CALL FOR POSTERS
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In addition to exhibiting, there are
many sponsorship opportunities for your company to maximize its
exposure and influence. They include conference specific
sponsorships, technology workshops, networking receptions,
delegate bags, etc. We are also ready to work with you in
customizing a solution to meet your specific marketing objectives.
Make a lasting impression as a thought leader by taking advantage
of these marketing tools.
The early rate for exhibitors is
July 18, 2003 - register to exhibit by that date and you will save
$225!
For more information on available
sponsorship packages and exhibit space please contact Angela
Parsons at 781-972-5467 or aparsons@healthtech.com
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TRAVEL INFORMATION
Special Airline Discounts Available
Special Zone and Discount Fares have been
established for this conference with United Airlines. Please
call United Airlines Meeting Reservation Desk at 800-521-4041
and reference ID#579YS.
HOTEL INFORMATION
Boston Park Plaza Hotel
64 Arlington Street
Boston, MA 02116
Phone: 617-426-2000 o Fax: 617-426-5545
Cut-off: Sept. 12, 2003
$189 single $199 double
Please call the hotel directly to
make your room reservation. Identify yourself as a Cambridge
Healthtech Institute conference attendee to receive the reduced
room rate. Reservations made after the cut-off date or after the
group room block has been filled (whichever comes first) will be
accepted on a space-and-rate-availability basis. Rooms are
limited, so please book early.
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